Altered functional connectivity in human brain networks has been reported in mood
disorders. A moderating hub between resting state networks (RSNs) and the medial temporal
lobe (MTL) is the parahippocampal cortex (PHC), where abnormal activity has been reported
in depressed patients and suicide attempters. Alterations in neuronal mitochondrial
function
may contribute to depression and suicidal behavior, however, little is known about
the
underlying molecular level changes in relevant structures. Specifically, expressional
changes
related to suicide have not been reported in the PHC. Here, we compared the protein
expression levels of genes encoding tricarboxylic acid (TCA) cycle enzymes in the
PHC of
suicide victims by reverse phase protein array (RPPA) and mRNA levels by RT-PCR. Postmortem
human brain samples were collected from 12 control and 10 suicide individuals. The
entorhinal cortex (EC), topographically anterior to the PHC in the parahippocampal
gyrus,
served as a control. RPPA analysis revealed that the protein levels of DLD, OGDH,
SDHB,
SUCLA2 and SUCLG2 subunits were significantly elevated in the PHC but not in the EC.
Accordingly, the mRNA levels of respective subunits were also increased. The subunits
with
altered levels participate in enzyme complexes participating in the oxidative decarboxylation
branch of glutamine catabolism. Our data hint on a potential role of glutaminolysis
in the PHC
in the pathophysiology of suicidal behavior.
Keywords:
suicide, parahippocampal cortex, reverse phase protein array, mitochondria, tricarboxylic
acid
cycle, glutaminolysis
